The antagonism between the essential divalent metals, calcium, magnesium, and zinc and the divalent metal carcinogens, lead, nickel and cadmium are under investigation in metabolic, chemical and carcinogenicity studies. Magnesium has been shown to inhibit lung adenoma formation in lead- and nickel-treated strain A mice, as well as cadmium- and nickel-induced sarcomas in rats. Part of the protection afforded by magnesium against the tumorigenic activity of cadmium and nickel is due to the diminished accumulation of the carcinogenic metal at the target site. In chemical studies cadmium binding to DNA was found to be inhibited by zinc, magnesium and calcium. Extension of the possible antagonistic effects of the physiologically essential divalent metals against tumor formation by nickel, lead, and cadmium in other target sites will be explored.